Certain forms of hyperlipidemia are associated with atherosclerosis. The pathophysiology and underlying biochemical defects associated with these disorders are, for the most part, poorly understood. For that reason, clinical classification and treatment are usually empirical. In this project, genetic forms of hyperlipidemia will be investigated in single families to eliminate heterogeneous study groups. Lipoprotein turnover studies and chemical cholesterol balance will be performed in affected subjects to search for consistent abnormalities in the metabolic parameters relating to lipoprotein and cholesterol metabolism. Particular emphasis will be placed on establishing the characteristic synthetic and catabolic rates for lipoproteins in the various genetic hyperlipidemias. Metabolic conversion of one lipoprotein to another will also be evaluated in the disease states. Finally, total body cholesterol excretion will be measured in the different disorders to see if lipoprotein turnover in any way relates to total cholesterol production in vivo. Whenever possible, the information obtained in vivo will be related to the known biochemical alterations observed in the specific form of hyperlipidemia under study.